HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture.

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.

Pyroptotic macrophages promote proliferation and chemotherapy resistance of peripheral T-cell lymphoma via TLR4 signaling pathway.

Peripheral T-cell lymphoma (PTCL) is a highly aggressive type of non-Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL-18. Upregulated TLR4 activated its downstream NF-κB anti-apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF-κB anti-apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In-depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.

MicroRNA-93-5p regulates odontogenic differentiation and dentin formation via KDM6B.

BACKGROUND: Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation. METHODS: The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin. RESULTS: The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3' untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin. CONCLUSIONS: MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.

Turning Polysaccharides into Injectable and Rapid Self-Healing Antibacterial Hydrogels for Antibacterial Treatment and Bacterial-Infected Wound Healing.

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria), as well as MRSA bacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSA and significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.

DNA-based nanosized functional ruthenium(II) complex as potential phosphorescent probe to track tumor cells.

Identifying tumor cells can be challenging due to cancer's complex and heterogeneous nature. Here, an efficacious phosphorescent probe that can precisely highlight tumor cells has been created. By combining the ruthenium(II) complex with oligonucleotides, we have developed a nanosized functional ruthenium(II) complex (Ru@DNA) with dimensions ranging from 300 to 500 nm. Our research demonstrates that Ru@DNA can readily traverse biomembranes via ATP-dependent endocytosis without carriers. Notably, the nanosized ruthenium(II) complex exhibits rapid and selective accumulation within tumor cells, possibly attributed to the nanoparticles' enhanced permeation and retention (EPR) effect. Ru@DNA can also effectively discern and label the transplanted cancer cells in the zebrafish model. Moreover, Ru@DNA is efficiently absorbed into the intestine and further distributed in the pancreas. Our findings underscore the potential of Ru@DNA as a DNA-based nanodevice derived from a functional ruthenium(II) complex. This innovative nanodevice holds promise as an efficient phosphorescent probe for both in vitro and in vivo imaging of living tumor cells.

Systematic Review of the Application of Computational Fluid Dynamics for Adult Aortic Diseases.

Background: Computational fluid dynamics (CFD) is a new medical method combining medicine and science. The aim of this study is to summarize and analyze the application of CFD in adult aortic diseases. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search in the PubMed, Cochrane Library and Chinese databases identified 47 highly relevant articles. Studies were included if they assessed biomechanical markers and their potential association with progression or rupture of aortic aneurysms or dissections. Results: There are no randomized controlled trials to examine the direct relationship between all biomechanical parameters and aortic disease progression or rupture. Wall stress and peak wall rupture risk can predict the risk of aortic aneurysm rupture using biomechanics, which is more accurate than the prediction based on "diameter" alone. Areas with lower time averaged wall shear stress (TAWSS) and higher oscillatory shear index (OSI) are at risk for further aortic expansion or dissection. Higher relative residence time (RRT) area can predict platelet activation and thrombosis. In addition, pressure, flow field and other indicators can also roughly predict the risk of aortic disease progression. Conclusions: Contemporary evidence suggests that CFD can provide additional hemodynamic parameters, which have the potential to predict the progression of aortic lesions, the effect of surgical intervention, and prognosis.

Neurosteroids: A novel promise for the treatment of stroke and post-stroke complications.

Stroke is the primary reason for death and disability worldwide, with few treatment strategies to date. Neurosteroids, which are natural molecules in the brain, have aroused great interest in the field of stroke. Neurosteroids are a kind of steroid that acts on the nervous system, and are synthesized in the mitochondria of neurons or glial cells using cholesterol or other steroidal precursors. Neurosteroids mainly include estrogen, progesterone (PROG), allopregnanolone, dehydroepiandrosterone (DHEA), and vitamin D (VD). Most of the preclinical studies have confirmed that neurosteroids can decrease the risk of stroke, and improve stroke outcomes. In the meantime, neurosteroids have been shown to have a positive therapeutic significance in some post-stroke complications, such as epilepsy, depression, anxiety, cardiac complications, movement disorders, and post-stroke pain. In this review, we report the historical background, modulatory mechanisms of neurosteroids in stroke and post-stroke complications, and emphasize on the application prospect of neurosteroids in stroke therapy.

Genome-wide identification of the histone acetyltransferase gene family in Triticum aestivum.

BACKGROUND: Histone acetylation is a ubiquitous and reversible post-translational modification in eukaryotes and prokaryotes that is co-regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). HAT activity is important for the modification of chromatin structure in eukaryotic cells, affecting gene transcription and thereby playing a crucial regulatory role in plant development. Comprehensive analyses of HAT genes have been performed in Arabidopsis thaliana, Oryza sativa, barley, grapes, tomato, litchi and Zea mays, but comparable identification and analyses have not been conducted in wheat (Triticum aestivum). RESULTS: In this study, 31 TaHATs were identified and divided into six groups with conserved gene structures and motif compositions. Phylogenetic analysis was performed to predict functional similarities between Arabidopsis thaliana, Oryza sativa and Triticum aestivum HAT genes. The TaHATs appeared to be regulated by cis-acting elements such as LTR and TC-rich repeats. The qRT-PCR analysis showed that the TaHATs were differentially expressed in multiple tissues. The TaHATs in expression also responded to temperature changes, and were all significantly upregulated after being infected by barley streak mosaic virus (BSMV), Chinese wheat mosaic virus (CWMV) and wheat yellow mosaic virus (WYMV). CONCLUSIONS: These results suggest that TaHATs may have specific roles in the response to viral infection and provide a basis for further study of TaHAT functions in T. aestivum plant immunity.

Insight into the divergent role of TRAIL in non-neoplastic neurological diseases.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor (TNF) superfamily which mainly induces apoptosis of tumour cells and transformed cell lines with no systemic toxicity, whereas they share high sequence homology with TNF and CD95L. These unique effects of TRAIL have made it an important molecule in oncology research. However, the research on TRAIL-related antineoplastic agents has lagged behind and has been limited by the extensive drug resistance in cancer cells. Given the several findings showing that TRAIL is involved in immune regulation and other pleiotropic biological effects in non-malignant cells, TRAIL and its receptors have attracted widespread attention from researchers. In the central nervous system (CNS), TRAIL is highly correlated with malignant tumours such as glioma and other non-neoplastic disorders such as acute brain injury, CNS infection and neurodegenerative disease. Many clinical and animal studies have revealed the dual roles of TRAIL in which it causes damage by inducing cell apoptosis, and confers protection by enhancing both pro- and non-apoptosis effects in different neurological disorders and at different sites or stages. Its pro-apoptotic effect produces a pro-survival effect that cannot be underestimated. This review extensively covers in vitro and in vivo experiments and clinical studies investigating TRAIL. It also provides a summary of the current knowledge on the TRAIL signalling pathway and its involvement in pathogenesis, diagnosis and therapeutics of CNS disorders as a basis for future research.

Measurement and spatiotemporal characteristics of China's green finance.

To study the extent of green finance development in China, this article constructs a green finance index system and employs the entropy value method to measure China's green finance by using a yearly provincial panel data from 2001 to 2020. The Thiel and Moran indices are then used to systematically analyze the temporal and spatial distribution of China's regional green finance. The findings are summarized as follows. Firstly, the overall green finance index in China experiences an upward trend. The development of green finance in the eastern region is superior to that in other regions in terms of absolute value and growth rate. Moreover, the differences in China's green finance index have shown an increasing trend over the last two decades, which is mostly contributed by the intra-regional differences. Finally, the inter-regional distribution of green finance index demonstrates that green finance development has a spatial spillover effect.

Characterization and Long-Term Prognosis of Patients with Different Phenotypes of Dilated Cardiomyopathy.

BACKGROUND: Long-term prognosis of dilated cardiomyopathy (DCM) in the Chinese population is lacking, and the left ventricular (LV) hypertrabeculation phenotype usually overlaps with DCM. OBJECTIVES: The study aims to investigate whether the presence of the LV hypertrabeculation phenotype confers additional adverse prognostic information for DCM patients. METHODS: We retrospectively reviewed all DCM patients (≥18 years of age at diagnosis) hospitalized in the Peking Union Medical College Hospital between September 2002 and September 2022. The eligible patients were divided into two groups based on echocardiography at diagnosis: the isolated DCM (n = 353), and DCM with the LV hypertrabeculation phenotype (n = 97). The primary endpoint was major adverse cardiac events (MACEs), and multivariate Cox hazards regression models were used to compare the endpoints between the two groups. RESULTS: During a mean follow-up time of 4.6 years, there was no significant difference in the primary endpoint between the isolated DCM and DCM with the LV hypertrabeculation phenotype (p = 0.19). The risk of MACEs in the first 5 years was significantly higher in DCM with the LV hypertrabeculation phenotype than isolated DCM (adjusted HR [95%CI]: 1.83 [1.21-2.77]) and after 5 years the effect of the LV hypertrabeculation phenotype as a prognostic attenuated. Subgroup analysis found a significant interaction for the incidence of MACEs between sex and DCM subtypes (p for interaction = 0.01). CONCLUSIONS: DCM with LV hypertrabeculation phenotypes had a higher early (first 5 years) risk of MACEs. For males, the presence of LV hypertrabeculation phenotypes might be an important clue for identifying high-risk DCM patients.

Antioxidant and antibacterial hydrogel formed by protocatechualdehyde-ferric iron complex and aminopolysaccharide for infected wound healing.

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe3+) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors.

Introduction: Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy. Methods: We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS. Results: The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0-32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710). Conclusion: The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

Analysis of nutrients in Apriona germari and treatment of diarrhea in mice fed with insect powder.

The insect larvae of Apriona germari, Apriona swainsoni and other closely related species are related to the insects that bore through the stems of the Caesalpinia decapetala. Because of therich nutritional as well as medicinal value of edible A. germari, it is often used to nourish the body, enhance immunity, and to treat ailments such as diarrhea. The soluble protein content of A. germari was determined using Kjeldahl and Soxhlet extraction methods. The crude fat content and the content of various fatty acids was determined by the normalization method, normalization method refers to that after the fat in the sample is extracted by hydrolysis ether solution, it is saponified and methylated under alkaline conditions to generate fatty acids and methyl esters, which are analyzed by capillary column gas chromatography and quantitatively measured by area normalization method. Amino acid content determined using an amino acid analyzer after acid hydrolysis showed 17 kinds of amino acids. A diarrhea mouse model was established by injecting a suspension of Escherichia coli into the abdominal cavity of mice. The mice were then fed with A. germari fodders at dose concentrations of 12%, 8%, 4% and 0%. The number of E. coli was determined from the intestinal tracts of mice; the activities of antioxidant enzymes and digestive enzymes in the serum were determined. Eleven kinds of fatty acids were detected in A. germari; unsaturated fatty acids accounted for 71.87% of the total fatty acids. A. germari is an edible resource insect with high nutritional value. Mice fed with A. germari showed an increase in the activity of antioxidant enzymes and digestive enzymes in the serum, which helped in the effective inhibition and reduction in the total number of intestinal bacteria and E. coli. The results indicate that A. germari has high nutritional value; A. germari also has a certain therapeutic effect on diarrhea caused by E. coli in mice.

Stem cells in central nervous system diseases: Promising therapeutic strategies.

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

Functional Outcome Analysis of Stereotactic Catheter Aspiration for Spontaneous Intracerebral Hemorrhage: Early or Late Hematoma Evacuation?

BACKGROUND: Minimally invasive stereotactic catheter aspiration becoming a promising surgical alternative for intracerebral hemorrhage (ICH) patients. Our goal is to determine the risk factors that lead to poor functional outcomes in patients undergoing this procedure. METHODS: Clinical data of 101 patients with stereotactic catheter ICH aspiration were retrospectively reviewed. Univariate and multiple logistic analyses were used to identify risk factors for poor outcomes 3 months and 1 year after discharge. Univariate analysis was used to compare the functional outcome between early (<48 h after ICH onset) and late hematoma evacuation (≥48 h after ICH onset) groups, as well as for the odd ratios assessment in terms of rebleeding. RESULTS: Independent factors for poor 3-month outcome included lobar ICH, ICH score > 2, rebleeding, and delayed hematoma evacuation. Factors for poor 1-year outcome included age > 60, GCS < 13, lobar ICH, and rebleeding. Early hematoma evacuation was linked to a lower likelihood of poor outcome both 3 months and 1 year post-discharge, but with higher risk of postoperative rebleeding. CONCLUSIONS: Lobar ICH and rebleeding independently predicted both poor short- and long-term outcomes in patients with stereotactic catheter ICH evacuation. Early hematoma evacuation with preoperative rebleeding risk evaluation may benefit patients with stereotactic catheter ICH evacuation.

Classification of Hepatocellular Carcinoma Based on N6-Methylandenosine-Related lncRNAs Profiling.

HCC is one of the most common types of malignancies worldwide and the fourth-leading cause of cancer deaths. Thus, there is an urgent need to search for novel targeted therapies in HCC. 186 m6a-related lncRNAs were screened for subsequent analysis. Two distinct m6A modification clusters were identified to be associated with the overall prognosis in TCGA-LIHC based on the m6A-related lncRNAs profiling, followed by univariate Cox regression analysis. In addition, four m6A-related lncRNAs prognostic signatures were developed and validated that could predict the OS of HCC patients, followed by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, four m6A-related lncRNAs were identified to be related to HCC prognosis. ESTIMATE was used to evaluate the stromal score, immune score, ESTIMATE score, and tumor purity of each HCC sample. ssGSEA was performed to identify the enrichment levels of 29 immune signatures in each sample. Finally, quantitative real-time polymerase chain reaction shown that KDM4A-AS1, BACE1-AS, and NRAV expressions were upregulated in HCC patients. We proved that our m6A-related lncRNAs signature had powerful and robust ability for predicting OS of different HCC subgroups.